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がん細胞におけるミトコンドリア由来活性酸素を介した3-Methyl pyruvateによる放射線感受性の増強

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タイトル: がん細胞におけるミトコンドリア由来活性酸素を介した3-Methyl pyruvateによる放射線感受性の増強
その他のタイトル: 3-Methyl pyruvate enhances the radiosensitivity through increase of mitochondria derivedreactive oxygen species in tumor cell lines
著者: 西田, 直哉 著作を一覧する
発行日: 2014年 3月25日
抄録: Considerable interest has recently been focused on the special characteristics of cancer metabolism, and several drugs designed to modulate cancer metabolism have been tested as potential anticancer agents. To date, however, very few studies have been conducted to investigate the combined effects of anticancer drugs and radiotherapy. In this study, to evaluate the role of mitochondria-derived reactive oxygen species (ROS) in the radiation-induced cell death of tumor cells, we have examined the effect of 3-methyl pyruvate (MP). MP is a membrane-permeable pyruvate derivative that is capable of activating mitochondrial energy metabolism, on human lung carcinoma A549 cells and murine squamous carcinoma SCCVII cells. Pretreatment with MP significantly enhanced radiation-induced cell death in both cell lines, and also led to increases in themitochondrial membrane potential, intracellular adenosine triphosphate content, and mitochondria-derived ROS production following the exposure of the cells to X-rays. In A549 cells, MP-induced radiosensitization was completely abolished by vitamin C. In contrast, it was partially abolished in SCCVII cells. These results therefore suggest that the treatment of the cells with MP induced radiosensitization via the production of excess mitochondria-derived ROS in tumor cells.
学位授与機関: Hokkaido University(北海道大学)
学位の報告番号: 甲第11283号
取得学位の種別: 博士
取得学位の分野: 獣医学
取得学位の審査委員: (主査) 教授 稲波 修, 教授 石塚 真由美, 准教授 佐藤 耕太, 准教授 山盛 徹
学位審査の研究科等: 獣医学研究科(獣医学専攻)
資料タイプ: theses (doctoral)
出現コレクション:獣医学研究科(Graduate School of Veterinary Medicine)
博士 (獣医学)


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